Postural tachycardia syndrome (POTS) is one of the most common forms of chronic orthostatic intolerance in the United States. This is a disabling disorder characterized by an excessive increase in heart rate upon standing that is accompanied by symptoms such as dizziness and fatigue. One of the most under appreciated and bothersome symptoms of POTS is impaired cognition or "brain fog," which occurs to a level that interferes with daily activities such as work and education. Despite this high impact, the reasons why POTS patients have problems with cognition are not well understood. This project will test the overall hypothesis that "brain fog" in POTS is related to increased activation of cognitive brain regions during mental tasks when compared with healthy subjects, and that this activation is exacerbated by in the presence of orthostatic stress.

A randomized, double blind, crossover study will be conducted to determine if there are differences in resting brain structure and blood oxygen perfusion in postural tachycardia syndrome (POTS) compared with healthy subjects, and to identify the pattern of brain activation produced by cognitive testing under resting conditions and in the presence of a physical challenge mimicking orthostatic stress (lower body negative pressure, LBNP). This is an outpatient study that requires a screening visit in the Clinical Research Center within the Penn State Hershey Medical Center, and if eligible, two study visits in the Penn State Center for Nuclear Magnetic Resonance Imaging involving blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) and a cognitive test while lying in a magnetic resonance imaging (MRI) scanner with the lower body placed in the LBNP chamber. The LBNP chamber applies suction to the lower body to pool blood in the legs and physiologically mimic what happens when standing up. Blood pressure, heart rate, and oxygen saturation will be measured throughout the study. A scan will be performed while at rest to look at the structure and blood oxygen perfusion in the brain. The LBNP or sham pressure will then be initiated, with the order determined randomly and the other stress applied at the second study visit. Once the appropriate level of pressure is achieved, brain oxygen perfusion will be measured and subjects will be asked to complete one test of cognitive function. At the end of the cognitive test, brain oxygen levels will be measured and the testing will end. The time inside the MRI scanner at each study visit will be approximately 45 minutes.

Inclusion Criteria:

• Men and women of all races or ethnicity
• Age 18-60
• Healthy volunteers or previously diagnosed with POTS by current consensus criteria (rise in heart rate of at least 30 beats/minute within 10 minutes of standing; absence of orthostatic hypotension defined as a drop in blood pressure greater than 20/10 mmHg within 3 minutes of standing; and presence of daily orthostatic symptoms for at least 6 months such as lightheadedness, dizziness, nausea, and palpitations).
• Healthy participants must have cognitive testing scores within normal range (defined by Stroop word-color test score between 40-70) and be able to tolerate lower body negative pressure.
• POTS participants must have either mild cognitive dysfunction (defined by Stroop word-color t-score <40 and >30) or normal cognitive function (defined by Stroop word-color test score between 40-70), and able to tolerate lower body negative pressure.
• Capable of giving informed consent
• Fluent in written and spoken English

Exclusion Criteria:

• Age <18 years or >60 years
• Pregnant or breastfeeding women
• Left handedness
• Require glasses for vision correction (contact lenses are okay)
• Current smokers
• Alcohol or drug abuse
• Recreational drug use (e.g. cannabis, heroin, cocaine)
• Other potential causes for tachycardia (e.g. prolonged bed rest, dehydration)
• Taking selective norepinephrine reuptake inhibitors or stimulant medications within the past 3 months as these may alter cognition
• Unable to tolerate an MRI scanner (e.g. claustrophobia, implanted metal)
• Unable to give or withdraw informed consent